Retroviruses, long associated with leukemia and sarcoma of animals, have recently been implicated as the etiological agents of human T cell leukemia and human acquired immune deficiency syndrome (AIDS). The identification of these agents makes it possible to consider various ways of prevention. The most promising approach is development of a vaccine that could be administered to individuals at risk. The vaccinia vector system has been shown to produce both humoral and cell mediated immunity against a variety of infectious agents. Since human retroviruses have not yet been shown to produce disease in animals, initial vaccine work must be done with animal retroviruses. Friend leukemia virus complex is a useful model system since it produces an acute disease in adult mice which can be prevented by repeated immunization with the envelope glycoprotein. The envelope gene of Friend murine leukemia virus (MuLV) was inserted into vaccinia virus under the control of a vaccinia virus promoter that is active at early and late times after infection. Pulse-labeling experiments indicated that an MuLV polypeptide of 85 kD was synthesized and subsequently processed to polypeptides of 70 kD and 15 kD. Immunofluorescence studies indicated that the 70 kD polypeptide was inserted into the cell membrane. Mice vaccinated with the recombinant virus produced antibodies to the MuLV envelope protein and were protected against the development of splenomegaly upon intravenous challenge with MuLV. A similar procedure was used to prepare vaccinia virus recombinants that express the envelope gene of HTLV-III, the causative agent of AIDS. Immunoblotting and immunoprecipitation studies indicated that the 160 kD polypeptide is synthesized and processed correctly. The ability of this recombinant to induce an immune response in experimental animals is under investigation.